tbuckley/cabot-search huggingface dataset:
Prospective comparison between provider’s assessment and geriatric assessment among older adults with gastroesophageal cancer.
Authors: Meghan Connors, Elizabeth A. Handorf, Caitlin R. Meeker, Kelly A. Filchner, Namrata Vijayvergia, Efrat Dotan
Journal: Journal of Clinical Oncology (2022)

e24013 Background: Geriatric Assessment (GA) can help oncologists determine fitness of their older patients for cancer therapy. Our objective was to identify gaps that exist in the care of older adults with gastroesophageal cancer (GEC). Methods: Patients age 65 or older with any stage of GEC were consented and completed a self-administered GA. The patient’s provider completed a baseline assessment (PA) and abnormalities detected by both assessments were centrally reviewed and compared. Geriatric domains assessed include functional status, nutrition, comorbidities, psychological distress, cognition, social support, chemotherapy toxicity risk, and financial toxicity. Any abnormalities found within an evaluated domain were considered in the analysis. Providers reviewed patient GA alongside indicated interventions and identified those they would implement. We compared the proportions detected/not detected by PA vs GA using McNemar’s test for paired data, and we measured agreement using Kappa statistics. This is an interim report of an ongoing trial with total accrual goal of 100 older adults with GEC. Results: 33 patients were enrolled at the time of the interim analysis, majority were male (22, 67%), median age 74 (65-91), with stage III (9, 50%) disease treated with combination chemotherapy (12, 36%). Cancer site was distributed between gastric (45%), esophageal (36%), GEJ (18%). 90% of patients had ECOG status 0 or 1. GA detected 164 abnormalities in geriatric domains, mean 5 per patient, and PA detected 104 abnormalities, mean 3 per patient (see Table). Significant difference in abnormality identification between GA and PA were seen in domains of nutrition, chemotherapy toxicity risk, financial toxicity and psychological distress. 37% of patients had abnormal TUG score and those patients were more likely to have other geriatric abnormalities detected by GA (6.2 vs 4.4). Providers for 28 patients (85%) indicated they would make at least one change, with the majority being referral to social work. Conclusions: Among older adults with gastroesophageal cancer, GA identifies more abnormalities as compared to routine provider’s assessment in most cases leading to important clinical interventions.[Table: see text]
First clinical application of the novel PSMA-11-derived hybrid molecule PSMA-914 for preoperative PET/CT imaging and fluorescence-guided surgery of prostate cancer
Authors: C.A. Jilg, A.C. Eder, M.A. Omrane, S. Stadlbauer, M. Roscher, W.Y. Khoder, C. Gratzke, K. Kopka, P.T. Meyer, J. Ruf
Journal: European Urology (2022)
Biomarker analysis of first-line camrelizumab plus apatinib in patients with advanced biliary tract cancers: Results from a phase II study.
Authors: Jian-hua Rao, Dong-sheng Chen, Yunjie Song
Journal: Journal of Clinical Oncology (2022)

e16164 Background: The prognosis of immunotherapy for patients with unresectable or metastatic biliary tract cancers (BTCs) was not very optimistic, exploring the potential biomarkers associated with tumor response in advanced BTCs may further improve the clinical benefits from immunotherapy. Methods: Fourteen advanced BTCs patients from the single-arm phase II study (ChiCTR2000034283) receiving camrelizumab (anti-PD-1 antibody) plus apatinib (VEGFR2 inhibitor) as first-line combination therapy, were included for the current biomarkers analysis. Exploratory points mainly focused on differentiated immune-related gene expression and immune pathway signatures using a 289-gene immune-related RNA panel sequencing on baseline tumor samples. Differential gene expression analysis was performed between responders (tumor regression) and non-responders (tumor extension) using Wilcoxon rank-sum test. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures. Results: Of all enrolled patients with clinical response evaluations, twelve patients had available RNA-sequencing data (6 responders vs. 6 non-responders) on baseline tumor samples. Differential gene expression analysis revealed a significantly higher BRCA2, RAD51, BRIP1 expression (p &lt; 0.001) and decreased TGF β 1, IT GAX, ITGB2 expression (p &lt; 0.001) in responder tumors compared with non-responder tumors. Differentiated genes were significantly enriched in receptor metabolic process pathway in responder tumors. Extensive analyses on immune cell types score were also calculated, CD8 positive T cells (p = 0.022) were significantly increased in baseline responder tumors, and Macrophages M2 cells (p = 0.008) were significantly increased in baseline non-responder tumors. Conclusions: Some differentially expressed genes and immune-related cell types were founded in defined groups, both immune- and tumor-intrinsic factors may be considered for validation in a larger study. Clinical trial information: ChiCTR2000034283.
The circSPON2/miR-331-3p axis regulates PRMT5, an epigenetic regulator of CAMK2N1 transcription and prostate cancer progression
Authors: Bing Yao, Sha Zhu, Xiyi Wei, Ming-Kun Chen, Yangkun Feng, Zhimin Li, Xinyu Xu, Yuwei Zhang, Yang Wang, Jingwan Zhou, Ningyuan Tang, Chengjian Ji, Peng Jiang, Shan-Chao Zhao, Chao Qin, Ninghan Feng
Journal: Molecular Cancer (2022)

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men, and its mechanism remains poorly understood. Therefore, it is urgent to discover potential novel diagnostic biomarkers and therapeutic targets that can potentially facilitate the development of efficient anticancer strategies.A series of functional in vitro and in vivo experiments were conducted to evaluate the biological behaviors of PCa cells. RNA pulldown, Western blot, luciferase reporter, immunohistochemistry and chromatin immunoprecipitation assays were applied to dissect the detailed underlying mechanisms. High-throughput sequencing was performed to screen for differentially expressed circRNAs in PCa and adjacent normal tissues.Upregulation of protein arginine methyltransferase 5 (PRMT5) is associated with poor progression-free survival and the activation of multiple signaling pathways in PCa. PRMT5 inhibits the transcription of CAMK2N1 by depositing the repressive histone marks H4R3me2s and H3R8me2s on the proximal promoter region of CAMK2N1, and results in malignant progression of PCa both in vitro and in vivo. Moreover, the expression of circSPON2, a candidate circRNA in PCa tissues identified by RNA-seq, was found to be associated with poor clinical outcomes in PCa patients. Further results showed that circSPON2 induced PCa cell proliferation and migration, and that the circSPON2-induced effects were counteracted by miR-331-3p. Particularly, circSPON2 acted as a competitive endogenous RNA (ceRNA) of miR-331-3p to attenuate the repressive effects of miR-331-3p on its downstream target PRMT5.Our findings showed that the epigenetic regulator PRMT5 aggravates PCa progression by inhibiting the transcription of CAMK2N1 and is modulated by the circSPON2/miR-331-3p axis, which may serve as a potential therapeutic target for patients with aggressive PCa.
Neoadjuvant chemo-immunotherapy increases tumor immune lymphocytes infiltration in resectable NSCLC.
Authors: Ziming Li, Tianxiang Chen, Fengcai Wen, Ding Zhang, Yanan Chen, Xiaochen Zhao
Journal: Journal of Clinical Oncology (2022)

e20573 Background: NCIT (neoadjuvant Chemo-immunotherapy treatment) has revolutionized the treatment of resectable NSCLC due to its better MPR (major pathologic response) rate and pCR (pathologic complete response) rate over neoadjuvant chemotherapy or immunotherapy. However, the intrinsic mechanism underlying this treatment remains unclear. In recent years, the immune microenvironment has attracted considerable attention in the field of immunotherapy. In this study, we explored the relationship between tumor immune lymphocytes (TILs), tertiary lymphoid structures (TLS), and response to NCIT in resectable NSCLC and the change in TILs before and after NCIT. Methods: Twenty-five patients with stage IIA-IIIC NSCLC who underwent surgery after NCIT were enrolled in this retrospective study. Multiplex immunofluorescence (mIF) staining and image analysis assays were performed on the samples collected before and after NCIT for each patient. Results: Among the enrolled patients, 10 achieved MPR or pCR which were defined as response group, whereas 15 did not respond well to NCIT which were defined as non-response group. The results of the mIF assays revealed that NCIT was associated with an increase in immune lymphocytes, including CD3+ (tumor, p = 0.23; stroma, p &lt; 0.01), CD4+ (tumor, p = 0.011; stroma, p &lt; 0.001), CD4+Foxp3+ (tumor, p = 0.63; stroma, p &lt; 0.001), CD8+ (tumor, p = 0.00031; stroma, p &lt; 0.001), CD8+PD-1+ (tumor, p = 0.13; stroma, p = 0.022), PD-L1+CD68+ (tumor, p = 0.85; stroma, p = 0.041), and TLS (tertiary lymphoid structures, p = 0.00027). The comparison of TIL between response group and non-response group revealed that CD3, FOXP3+, and CD8+PD-1+ may serve as predictors of the response to neoadjuvant immunotherapy. Conclusions: To our knowledge, this is the first study to explore the relationship between TILs, TLS, and response to NCIT and TIL changes during NCIT in resectable Chinese NSCLC. In resectable NSCLC, the infiltration of immune cells before NCIT was correlated with the pathologic complete response, which enhanced the TILs as a promising predictor for selecting patients who were more likely to benefit from NCIT.
LINC-14. A single center retrospective analysis of pediatric pineoblastoma in Beijing
Authors: Miao Li, Shuxu Du, Yanling Sun, Shumei Wang, Wanshui Wu, Liming Sun
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: To explore the clinical characteristics and outcome in children with pineoblastoma in Beijing. METHODS: Clinical data of 18 pediatric patients with newly diagnosed pineoblastoma admitted to Beijing Shijitan Hospital between January 2014 and November 2021 were retrospectively analyzed. The diagnoses were confirmed by pathology. RESULTS: Male/female ratio=8:1. The median age at diagnosis was 4.7 (range, 0.2-12.6) years, with 2 cases in infancy, and 13 cases ≥ 3 years. The symptoms at diagnosis included headache (31%), vomiting (29%), convulsions (9%), strabismus (9%), nausea (6%), etc. Four patients experienced metastasis at diagnosis. Ki-67 index was under 30% in 5 cases, 30-80% and ≥80% in 10 and 2 cases, respectively. All were treated with surgery, and 12 children underwent gross total resection (GTR). Seventeen cases were administered both radiotherapy and chemotherapy, with one case only radiotherapy followed by surgery. Median follow-up time was 54 months. Nine patients developed a recurrence and 2 patients died at last follow-up. The 1-year/3-year progression-free survival (PFS) and overall survival (OS) were (77.8±10.5/11.1±10.5)%, and (100/90.9±8.7) %, respectively. The 3-year OS of boys (93.8%) was higher than that of girls (50.0%); and also higher in cases with GTR (91.7%) than STR (83.3%). However, the differences were not significant in the above two groups. The children with Ki-67 index ≥80% had worse 3-year OS than those&amp;lt;80% (χ2=8.000, P=0.005). The median PFS of children treated under the order of craniospinal irradiation followed by chemotherapy was better than that of the inverse order (29m vs 13m, χ2=6.528, P=0.011).CONCLUSION: Pineoblastoma is rare and often fatal, but with better OS in our center, although the PFS is dismal. Boys, GTR resections, and Ki-67 index &amp;lt;80% tends to have better OS, and the order of irradiation followed by chemotherapy tends to have better PFS. Keywords: pineoblastoma; therapy; survival
A real-world experience of TCH (docetaxel/carboplatin/trastuzumab) regimen in early, locally advanced and oligometastatic HER2 positive breast cancer from tertiary care center in North India.
Authors: Anshul Gupta, Ajay Gogia, Hari Krishna Raju Sagiraju, S.V.S. Deo, Ritu Gupta, Sandeep Mathur, Dayanand Sharma
Journal: Journal of Clinical Oncology (2022)

e12505 Background: In HER2 positive breast cancer, TCH is a safe and efficacious anthracycline free regimen used as both adjuvant and neoadjuvant modality. Three is scarcity of data regarding its long term safety and efficacy from India. Methods: This retrospective study comprised of 210HER2 positive breast cancer female patients treated with TCH [docetaxel (75mg/m 2 ), carboplatin (AUC=6) and trastuzumab (8mg/kg loading followed by 6mg/kg) q 21 days with GSF prophylaxis] protocol for 6 cycles at our centre between Jan 2014 and Dec 2021. All eligible patients received maintenance trastuzumab, hormonal therapy and radiotherapy as per institutional protocol. The information regarding baseline clinico-demographic characteristics, treatment details, outcomes and toxicities were collected and evaluated. Results: The median age was 49 years (23-72), 113 (53.8%) were post-menopausal and 100 (47.6%) were Estrogen receptor/Progesterone receptor positive. Sixty-eight (32.4%) patients were stage I and II, 112 (53.3%) stage III and 30 (14.3%) were oligometastatic. TCH regimen was given as neoadjuvant chemotherapy (NACT) in 130 (61.9%) patients and as adjuvant chemotherapy in 80 (38.1%) patients. Of the patients receiving NACT, 114 (87.6%) patients underwent surgery. Twenty-two (19.3%) patients underwent breast conservation surgery and 92 (80.7%) underwent modified radical mastectomy. Over the study period, 62 (29.5%) patients had progression of the disease and 22 (10.5%) patients died. With a median follow up of 31.9 months, 3-year disease free survival (DFS) was 63.5% and overall survival (OS) was 90.8%. Median DFS was 31 months in patients with node positive disease and was not reached in patients with node positive disease. Of the patients who received NACT, pathologic complete response (pCR) was recorded in 42 (36.8%) patients. Three-year DFS was 59.1% in patients who achieved pCR and 44.8% in those who did not achieve pCR. Any grade 3/4 toxicity was seen in 26.7% patients which caused dose modification in 13.9% patients. The most common grade 3/4 hematological toxicity was anemia (15.1%) and thrombocytopenia (10.4%), while non-hematological toxicity was diarrhea (11.6%). Febrile neutropenia was seen in 4 (1.9%) patients. Four patients (1.9%) had reversible decrease in cardiac left ventricular ejection fraction. Conclusions: Anthracycline free TCH regimen is an effective and safe regimen for use in curative (adjuvant and neoadjuvant) setting for HER2 positive breast cancer in Indian women with outcomes comparable to the anthracycline based regimens reported in literature.
Once-Weekly Exenatide in Youth With Type 2 Diabetes
Authors: William V. Tamborlane, Raafat Bishai, David Geller, Naim Shehadeh, Dalia Al-Abdulrazzaq, Evelina Mánica Vazquez, Eva Karoly, Tünde Troja, Orlando Doehring, Debra Carter, John Monyak, C. David Sjöström
Journal: Diabetes Care (2022)

Approved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated.Participants (aged 10 to <18 years) were randomized (5:2) to once-weekly exenatide 2 mg or placebo, respectively. The primary efficacy end point was change in glycated hemoglobin from baseline to week 24. Secondary efficacy end points were also evaluated, and the frequency of adverse events (AEs) was assessed.A total of 83 participants were randomized (exenatide, 59; placebo, 24) and 72 completed 24-week treatment (exenatide, 49; placebo, 23). At 24 weeks, the least squares mean change in glycated hemoglobin was -0.36% for the exenatide and +0.49% for the placebo groups (between-group difference, -0.85%; 95% CI -1.51, -0.19; P = 0.012). Nonsignificant least squares mean differences from baseline to 24 weeks favoring exenatide were observed: fasting glucose -21.6 mg/dL (-49.0, 5.7; P = 0.119), systolic blood pressure -2.8 mmHg (-8.0, 2.4; P = 0.284), and body weight -1.22 kg (-3.59, 1.15; P = 0.307). AEs occurred in 36 (61.0%) and 17 (73.9%) participants in the exenatide and placebo groups, respectively.In youth with type 2 diabetes suboptimally controlled with current treatments, once-weekly exenatide reduced glycated hemoglobin at 24 weeks and was well tolerated.
Mitochondrial function after endogenous glutathione synthesis stimulation in old rats heart
Authors: I Okhai, R Fedichkina, Y Goshovska, V Sagach
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Aging is accompanied by alterations mitochondrial function, and decreasing mitochondrial membrane potential (Δψm) amid increasing ROS/RNS. Mitochondrial disfunction is one of the cause of age-relating cardiovascular deseases development. Previously, we showed that stimulation synthesis of antioxidant glutathione (using DL-propargylglycine (PAG) + L-cysteine) provided complete restoration of the heart and mitochondrial function, reduced ROS levels at ischemia-reperfusion model in adult rats. The aim was to investigate whether PAG+L-cysteine stimulated glutathione synthesis in old rats, and cardiac Δψm, NOx (nitrite plus nitrate) and ROS production at endogenous stimulation glutathione synthesis. Stimulation of glutathione synthesis was performed by combined pretreatment with 11.3 mg/kg PAG and 120 mg/kg L-cysteine injected intraperitoneally 40 and 30 min before sacrificing. Langendorff isolated rat hearts were underwent 20 min perfusion. Cardiac mitochondria were isolated and tested for respiration rate and Δψm with TPMP+-selective electrode. Proton-leak was titrated with malonate addition. Glutathione level was measured by Ellman's reagent. Generation rate of superoxide radical and hydrogen peroxide, malondialdehyde and NOx levels, iNOS and cNOS (inducible and constitutive nitric oxide synthase) activity was determined spectrophotometrically in heart tissue. Pre-administration of PAG+L-cysteine to old rats increased the reduced glutathione level by 51.4%, P&amp;lt;0.05; significantly increased Δψm (P&amp;lt;0.01) and simultaneously decreased the rate of oxygen consumption by mitochondria (P &amp;lt;0.001); the proton-leak curve shifted to the right. It indicates improving the mitochondrial efficiency. At the same time, ROS generation was reduced by 48.2% and 21.7% for superoxide radical and hydrogen peroxide correspondingly, P&amp;lt;0.01. Malondialdehyde level dropped almost twice (P&amp;lt;0.01) too. Quantity NOx falled off by 24.5% with 52.5% decreased activity of iNOS and increased activity cNOS by 2.2 times, P&amp;lt;0.01. The reducing superoxide production and this condition of NO system may indicate of increase the coupling cNOS and ability heart to relax. Thus, endogenous glutathione synthesis stimulation in conditions of aging caused increasing Δψm and improved respiratory chain efficacy. The redox balance and metabolism of nitric oxide were normalized in rat heart.
Remote patient monitoring (RPM) through smartphone application in community oncology practice.
Authors: Rayna Kuthiala, Bijoy Pankaj Telivala, Tejas Karawadia
Journal: Journal of Clinical Oncology (2022)

e18828 Background: Patients with cancer receiving treatment can have symptoms related to their disease or treatment. Early recognition and appropriate intervention of these symptoms can lead to fewer emergency room visits and fewer hospitalizations with significant reduction in healthcare costs. Earlier treatment of symptoms leads to more adherence to treatment. We present data regarding reduction in healthcare costs after implementation of remote patient monitoring in our community oncology practice with 13 oncology practice sites and 29 medical oncologists in Jacksonville, Florida. Methods: We implemented RPM through a smartphone application at all our practice sites starting September 1,2021. We collected data regarding number of patients on active therapy who required inpatient admissions during the 3-month period from 9/1/2021 to 11/30/21 . We documented the number of admissions during this 3-month period in 2020, prior to implementation of RPM followed by number of admissions during the same period of time in 2021 after the implementation of RPM. The numerical difference in admissions was then multiplied by average cost of hospitalization for adult cancer patients to calculate the healthcare cost savings. Results: During the 3-month period in 2020 without RPM, there were 234 inpatient admissions. During the same time frame in 2021, after implementation of RPM, there were 199 admissions. The implementation of RPM, showed a 15 % reduction in number of inpatient admissions. Average cost of inpatient stay for a cancer patient is $22,100 as per the data from healthcare cost and utilization project. This would translate to $773,500 over 3-month period and approximately $3 million annual healthcare cost savings. The annual cost of implementation of RPM in our practice was $350,000 which includes cost of smartphone application and the required clinical staff. Conclusions: Remote patient monitoring through smartphone application can be effectively implemented in community oncology practice with significant reduction in healthcare costs. Not only does it save money, it helps improve patient experience and adherence to treatment. We will continue to collect data to see if the trend continues.